TY - JOUR
T1 - The clinical significance of molecular response in indolent follicular lymphomas
AU - López-Guillermo, Armando
AU - Cabanillas, Fernando
AU - McLaughlin, Peter
AU - Smith, Terry
AU - Hagemeister, Fredrick
AU - Rodríguez, María A.
AU - Romaguera, Jorge E.
AU - Younes, Anas
AU - Sarris, Andreas H.
AU - Preti, H. Alejandro
AU - Pugh, William
AU - Lee, Ming Seng
PY - 1998/4/15
Y1 - 1998/4/15
N2 - Most patients with follicular lymphoma (FL) achieve a complete response (CR) after treatment, but eventually most of them, particularly those with stage IV, relapse due to minimal residual disease (MRD). The t(14;18) gives rise to a rearrangement of the bcl-2 oncogene that constitutes an excellent target for detection of MRD by polymerase chain reaction (PCR). One hundred ninety-four previously untreated patients with indolent FL and detectable bcl-2 rearrangement were studied. The PCR assay was used to detect bcl-2- rearranged cells in blood and marrow before and after treatment. Molecular response rate was 37%, 53%, 56%, and 66% at 3 to 5, 6 to 8, 9 to 14, and 15 to 18 months from the start of therapy, respectively. Although molecular response was higher among clinical CRs, one third of partial responders at 3 to 5 months also achieved a molecular response. Patients who achieved a molecular response during the first year of treatment had a significantly longer failure-free survival (FFS) than those who did not (4-year FFS: 76% v 38%, respectively; P < .001). Similar results were also observed in the subset of patients in clinical CR 1 year after treatment. By multivariate analysis, β2-microglobulin (β2-M; P < .01), and molecular response (P < .001) were the most important variables associated with outcome. When we combined β2-M and molecular response, three prognostic groups emerged: (1) low β2-M and molecular responders, (2) low β2-M and nonresponders or high β2-M and responders, and (3) high β2-M and nonresponders. The 4-year FFS of these 3 groups were 86%, 65%, and 23%, respectively. Finally, patients who achieved molecular response and sustained it had better FFS than those who either reverted back to PCR-positive or who never achieved molecular response. Serial PCR analysis to determine the molecular response in FL correlates well with outcome especially when combined with pretreatment β2- M.
AB - Most patients with follicular lymphoma (FL) achieve a complete response (CR) after treatment, but eventually most of them, particularly those with stage IV, relapse due to minimal residual disease (MRD). The t(14;18) gives rise to a rearrangement of the bcl-2 oncogene that constitutes an excellent target for detection of MRD by polymerase chain reaction (PCR). One hundred ninety-four previously untreated patients with indolent FL and detectable bcl-2 rearrangement were studied. The PCR assay was used to detect bcl-2- rearranged cells in blood and marrow before and after treatment. Molecular response rate was 37%, 53%, 56%, and 66% at 3 to 5, 6 to 8, 9 to 14, and 15 to 18 months from the start of therapy, respectively. Although molecular response was higher among clinical CRs, one third of partial responders at 3 to 5 months also achieved a molecular response. Patients who achieved a molecular response during the first year of treatment had a significantly longer failure-free survival (FFS) than those who did not (4-year FFS: 76% v 38%, respectively; P < .001). Similar results were also observed in the subset of patients in clinical CR 1 year after treatment. By multivariate analysis, β2-microglobulin (β2-M; P < .01), and molecular response (P < .001) were the most important variables associated with outcome. When we combined β2-M and molecular response, three prognostic groups emerged: (1) low β2-M and molecular responders, (2) low β2-M and nonresponders or high β2-M and responders, and (3) high β2-M and nonresponders. The 4-year FFS of these 3 groups were 86%, 65%, and 23%, respectively. Finally, patients who achieved molecular response and sustained it had better FFS than those who either reverted back to PCR-positive or who never achieved molecular response. Serial PCR analysis to determine the molecular response in FL correlates well with outcome especially when combined with pretreatment β2- M.
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U2 - 10.1182/blood.v91.8.2955.2955_2955_2960
DO - 10.1182/blood.v91.8.2955.2955_2955_2960
M3 - Article
C2 - 9531606
AN - SCOPUS:2642590949
SN - 0006-4971
VL - 91
SP - 2955
EP - 2960
JO - Blood
JF - Blood
IS - 8
ER -